Some in vivo and in vitro properties of various fractions of Pimelea trichostachya.

Various fractions of alcoholic extract of Pimelea trichostachya were prepared and three of these were compared in terms of (a) ability to produce sustained contraction of spiral muscle of bovine pulmonary vein in vitro, (b) LD50 values in mice by intraperitoneal injection and (c) acute toxicity by intravenous injection into calves. Good agreement was observed between activity of the fractions in all three systems, thus providing further evidence for the role of pulmonary venous hypertension in the pathogenesis of at least part of the syndrome of Pimelea poisoning in the bovine. The most toxic of the fractions was shown by chronic intoxication of a calf to be capable of producing most of the features of the natural disease.

Anthraquinone pigments from Phoma foveata Foister.

1. Suitable conditions have been determined for growing the fungus Phoma foveata in culture for optimum production of pigments. 2. The pigments have been extracted and fractionated according to their solubility in aqueous bicarbonate, carbonate and alkali. 3. The carbonate- and alkali-soluble pigments have been further separated by chromatography and shown to consist of anthraquinone derivatives. 4. The alkali-soluble fraction, which comprised the bulk of the pigment, consists of pachybasin (1-hydroxy-3-methylanthraquinone; II) and chrysophanol (1,8-dihydroxy-3-methylanthraquinone; III) by comparison with authentic samples. 5. The carbonate-soluble fraction contains emodin (1,6,8-trihydroxy-3-methylanthraquinone; V) and a hitherto unrecorded pigment for which the name phomarin and the structure 1,6-dihydroxy-3-methylanthraquinone (IV) are put forward. 6. The identification of emodin and the structural determination of phomarin are based largely on their ultraviolet, visible, infrared, nuclear-magnetic-resonance and mass spectra.

Biogenesis of proteaceous alkaloids.

A scheme is presented which outlines the possible mode of biogenesis of alkaloids so far reported from the proteaceous plants Bellendena montana and Agastachys odorata (both from Tasmania), Darlingia darlingiana and D. ferruginea (from Queensland) and Knightia deplanchei and K. strobilina (from New Caledonia).

Bis(benzylisoquinoline) analogs of tetrandrine block L-type calcium channels: evidence for interaction at the diltiazem-binding site.

Bis(benzylisoquinoline) alkaloids block Ca2+ uptake through the L-type Ca2+ channel and modulate binding of ligands to four distinct sites (dihydropyridine, benzothiazepine, aralkylamine, and (diphenylbutyl)piperidine) in the Ca2+ entry blocker receptor complex of the channel. These alkaloids are structural analogs of tetrandrine, which has previously been demonstrated to block the L-type Ca2+ channel through interaction at the benzothiazepine (diltiazem) site (King et al., 1988). Different alkaloid conformational classes display either alpha-beta, beta-alpha, alpha-alpha, or beta-beta stereochemistry at the two chiral isoquinoline carbons. Compounds from all four classes were tested for their ability to interact with Ca2+ entry blocker ligands. All analogs completely inhibit diltiazem binding, but many only partially inhibit D-600 and fluspirilene binding. For dihydropyridine binding, the compounds show either stimulation or inhibition or exhibit no effect. This profile is quite different from the interaction displayed by diltiazem or tetrandrine. Scatchard analyses show effects predominantly on Kd for diltiazem, D-600, and PN200-110 binding. Representative conformers do not effect diltiazem dissociation rates but alter dissociation kinetics of ligands which bind to the other three sites. A correlation of the ability of these compounds to inhibit Ca2+ uptake through the L-type Ca2+ channel in GH3 cells exists only with their inhibition of diltiazem binding but not with inhibition of binding of ligands representing other classes of Ca2+ entry blockers. These data, taken together, indicate that a variety of bis(benzylisoquinoline) congeners act to block the L-type Ca2+ channel by binding to the benzothiazepine site on the channel.(ABSTRACT TRUNCATED AT 250 WORDS)